The Impact of Adversity on Body Mass Index as Veterans Transition to Civilian Life.

INTRODUCTION: The impact of adverse childhood experiences (ACEs), warfare exposure, and mental health symptoms upon changes in body mass index (BMI) were examined in a large U.S. post-9/11 veteran sample to assess gender-specific changes in BMI within the first 2½ years after military service. MATERIALS AND METHODS: Data were collected with institutional approval in 6 waves between 2016 and 2019 from veterans who (1) separated from active duty component service branches (i.e., Army, Navy, Air Force, and Marine Corps) or National Guard or Reserve or (2) deactivated from active duty status after serving in a National Guard or Reserve component. Veterans self-reported height and weight at separation/deactivation at wave 2, and weight was asked at each subsequent wave. Multilevel growth model analyses estimated the relationship between ACEs, warfare exposure, and mental health symptoms and BMI for males and females. Weighted wave 5 analyses were conducted to ensure the sample was calibrated for nonresponse based on wave 1 and the full sample (n = 48,965) for each cross-classification of the weighting variables of gender, rank, and branch. RESULTS: Approximately one-third of the veterans reported a normal BMI at separation/deactivation in comparison to being overweight (51%) or obese (20%). Twenty-six percent of male veterans had a normal BMI in contrast to almost half of the female veterans. Male veterans who experienced 3-7 ACEs had a higher BMI (0.74) compared to male veterans without any ACEs, where a BMI increase of 0.08 per year was reported. Female veterans who experienced 1-2 ACEs had a higher BMI (0.89) compared to female veterans without ACEs. Male veterans who engaged in warfare (e.g., combat patrols and firing a weapon at enemy combatants) and experienced corollaries (i.e., consequences of combat) or who experienced corollaries alone (e.g., saw refugees who lost their homes/belongings) had higher BMIs (1.14 and 0.82, respectively) compared to male veterans without warfare exposure. Female veterans who experienced corollaries had a higher BMI (0.94) compared to female veterans with no warfare exposure. Female veterans who experienced warfare (i.e., corollaries and combat) had a higher BMI (0.71) compared to female veterans with no warfare exposure. Male veterans who screened positive for likely post-traumatic stress disorder (PTSD) or depressive symptoms had a higher BMI (1.01 and 0.52, respectively) compared to male veterans who did not screen positive. Male veterans who screened positive for likely PTSD increased their BMI by 0.10 per year. Male veterans who screened positive for both likely PTSD and depressive symptoms had a higher BMI (1.32) compared to male veterans who did not screen positive, and they increased their BMI by 0.21 per year. Female veterans who screened positive for likely PTSD and depressive symptoms had a higher BMI (0.78) and increased their BMI by 0.25 per year compared to female veterans who did not screen positive. CONCLUSIONS: Boosting veterans' and service members' mental and emotional healing from childhood and warfare adversities through sound health promotion policies and increased access to evidence-informed interventions is imperative for optimal body weight and physical health.

Viral gene drive spread during herpes simplex virus 1 infection in mice.

Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we report on a viral gene drive against human herpes simplex virus 1 (HSV-1) and show that it propagates efficiently in cell culture and during HSV-1 infection in mice. We describe high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progresses from the site of inoculation to the peripheral and central nervous systems. In addition, we show evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicate that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study shows that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.

Combining single-molecule and structural studies reveals protein and DNA conformations and assemblies that govern DNA mismatch repair.

DNA mismatch repair (MMR) requires coordinated sequential actions of multiple proteins during a window of time after the replication apparatus makes an error and before the newly synthesized DNA undergoes chromosome compaction and/or methylation of dGATC sites in some γ-proteobacteria. In this review, we focus on the steps carried out by MutS and MutL homologs that initiate repair. We connect new structural data to early and recent single-molecule FRET and atomic force microscopy (AFM) studies to reveal insights into how signaling within the MMR cascade connects MutS homolog recognition of a mismatch to downstream repair. We present unified models of MMR initiation that account for the differences in the strand discrimination signals between methyl- and non-methyl-directed MMR.

Fads2 knockout mice reveal that ALA prevention of hepatic steatosis is dependent on delta-6 desaturase activity.

The production of the omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA) relies on the delta-6 desaturase (D6D) enzyme encoded by the Fads2 gene. While EPA and DHA reduce hepatic triacylglycerol (TAG) storage and regulate lipogenesis, the independent impact of ALA is less understood. To address this gap in knowledge, hepatic fatty acid metabolism was investigated in male wildtype (WT) and Fads2 knockout (KO) mice fed diets (16% kcal from fat) containing either lard (no n-3 LCPUFA), flaxseed oil (ALA rich), or menhaden oil (EPA/DHA rich) for 21 weeks. Fat content and composition, as well as markers of lipogenesis, glyceroneogenesis, and TAG synthesis, were analyzed using histology, gas chromatography, and reverse transcription quantitative PCR (RT-qPCR). Mice fed the menhaden diet had significantly lower hepatic TAG compared to both lard- and flax-fed mice, concomitant with changes in n-3 and n-6 LCPUFA in both TAG and phospholipid (PL) fractions (all p < 0.05). Flax-fed WT mice had lower liver TAG content compared to their KO counterparts. Menhaden-fed mice had significantly lower expression of key lipogenic (Scd1, Srebp-1c, Fasn, Fads1, Fads2), glyceroneogenic (Pck1), and TAG synthesis (Agpat3) genes compared to lard, with flax-fed mice showing some intermediate effects. Gene expression effects were independent of D6D activity, since no differences were detected between WT and KO mice fed the same diet. This study demonstrates that EPA/DHA and not ALA itself is critical for the prevention of hepatic steatosis.

Bayesian statistical concepts with examples from rodent toxicology studies.

The theory and practice of statistics comprises two main schools of thought: frequentist statistics and Bayesian statistics. Frequentist methods are most commonly used to analyze animal-based laboratory data, while Bayesian statistical methods have been implemented less widely and may be relatively unfamiliar to practitioners in experimental science. This paper provides a high-level overview of Bayesian statistics and how they compare with frequentist methods. Using examples in rodent toxicity research, we argue that Bayesian methods have much to offer laboratory animal researchers. We advocate for increased attention to and adoption of Bayesian methods in laboratory animal research. Bayesian statistical theory, methods, software, and education have advanced significantly in the last 30 years, making these tools more accessible than ever.

Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life. METHODS: We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations). RESULTS: The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash. CONCLUSIONS: Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).

Comparative analysis of LAG3 antibodies shows differential binding patterns by flow cytometry.

BACKGROUND: LAG3 is an immune checkpoint molecule with emerging therapeutic use. Expression of LAG3 is well studied on T cells, but the proportion of LAG3-expressing cells varies greatly by study and its comparative expression between non-T cells is lacking. METHODS/OBJECTIVES: This study uses flow cytometry to compare surface LAG3 expression between T cells, NK cells, B cells, pDCs and monocytes of healthy donors. This study also compares three monoclonal LAG3 antibodies to a commonly used polyclonal LAG3 antibody on ex vivo and PHA-blasts from healthy donors and LAG3+ and LAG3- cell lines. RESULTS: LAG3 was most highly expressed on classical and intermediate monocytes (25 % and 32 %, respectively), while LAG3 expression on B cells, NK cells and iNKT cells was negligible. Notably, the polyclonal antibody stained a higher proportion of all cell types than the monoclonal antibodies, which had similar staining patterns to one another. Further study using LAG3+ and LAG3- cell lines showed greater specificity and similar sensitivity of the monoclonal antibody T47-530 than the polyclonal antibody. CONCLUSION: Monocytes may represent an unappreciated source of LAG3 and target of LAG3 checkpoint inhibitors. Furthermore, the discrepancies between monoclonal and polyclonal LAG3 antibodies warrants consideration when designing future studies and interpreting past studies, and may explain discrepancies in the literature.

Generalizability of heat-related health risk associations observed in a large healthcare claims database of patients with commercial health insurance.

BACKGROUND: Extreme ambient heat is unambiguously associated with higher risk of illness and death. The Optum Labs Data Warehouse (OLDW), a database of medical claims from US-based patients with commercial or Medicare Advantage health insurance, has been used to quantify heat-related health impacts. Whether results for the insured sub-population are generalizable to the broader population has to our knowledge not been documented. We sought to address this question, for the US population in California from 2012 to 2019. METHODS: We examined changes in daily rates of emergency department (ED) encounters and in-patient hospitalization encounters for all-causes, heat-related outcomes, renal disease, mental/behavioral disorders, cardiovascular disease, and respiratory disease. OLDW was the source for health data for insured individuals in California, and health data for the broader population were gathered from the California Department of Health Care Access and Information (HCAI). We defined extreme heat exposure as any day in a group of 2 or more days with maximum temperatures exceeding the county-specific 97.5 th percentile and used a space-time-stratified case-crossover design to assess and compare the impacts of heat on health. RESULTS: Average incidence rates of medical encounters differed by dataset. However, rate ratios for ED encounters were similar across datasets for all causes (ratio of incidence rate ratios (rIRR) = 0.989; 95% confidence interval (CI) = 0.973, 1.011), heat-related causes (rIRR = 1.080; 95% CI = 0.999, 1.168), renal disease (rIRR = 0.963; 95% CI = 0.718, 1.292), and mental health disorders (rIRR = 1.098; 95% CI = 1.004, 1.201). Rate ratios for inpatient encounters were also similar. CONCLUSIONS: This work presents evidence that OLDW can continue to be a resource for estimating the health impacts of extreme heat.

The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

A Large Harmonized Upper and Lower Limb Accelerometry Dataset: A Resource for Rehabilitation Scientists.

Wearable sensors can measure movement in daily life, an outcome that is salient to patients, and have been critical to accelerating progress in rehabilitation research and practice. However, collecting and processing sensor data is burdensome, leaving many scientists with limited access to such data. To address these challenges, we present a harmonized, wearable sensor dataset that combines 2,885 recording days of sensor data from the upper and lower limbs from eight studies. The dataset includes 790 individuals ages 0 - 90, nearly equal sex proportions (53% male, 47% female), and representation from a range of demographic backgrounds (69.4% White, 24.9% Black, 1.8% Asian) and clinical conditions (46% neurotypical, 31% stroke, 7% Parkinson's disease, 6% orthopedic conditions, and others). The dataset is publicly available and accompanied by open source code and an app that allows for interaction with the data. This dataset will facilitate the use of sensor data to advance rehabilitation research and practice, improve the reproducibility and replicability of wearable sensor studies, and minimize costs and duplicated scientific efforts.

Motor competence is related to acquisition of error-based but not reinforcement learning in children ages 6 to 12.

Background: An essential component of childhood development is increasing motor competence. Poor motor learning is often thought to underlie impaired motor competence, but this link is unclear in previous studies. Aims: Our aim was to test the relationship between motor competence and motor learning in the acquisition phase. Both reinforcement learning (RL) and error-based learning (EBL) were tested. We hypothesized that slower RL and slower EBL acquisition rates would relate to lower motor competence. Methods and procedures: Eighty-six participants ages 6-12 performed a target throwing task under RL and EBL conditions. The Movement Assessment Battery for Children - 2nd edition (MABC-2) provided a measure of motor competence. We assessed EBL and RL acquisition rates, baseline variability, and baseline bias from the throwing task. Outcomes and results: In a multiple linear regression model, baseline variability (ß = -0.49, p = <0.001) and the EBL acquisition rate (ß = -0.24, p = 0.018) significantly explained the MABC-2 score. Participants with higher baseline variability and slower EBL acquisition had lower motor competence scores. The RL acquisition rate was independent of MABC-2 score suggesting that RL may be less of a contributor to poor motor competence. Conclusions and implications: Children with slower EBL acquisition had lower motor competence scores but RL acquisition was unrelated to the level of motor competence. Emphasizing the unrelated reinforcement mechanisms over error-based mechanisms during motor skill interventions may help children with poor motor competence better acquire new motor skills.

Synergistic Effect of Laser, Water Vapor, and Electron-Beam on the Degradation of Quasi-Two-Dimensional Ruddlesden-Popper Perovskite Flakes.

Understanding the effects of laser light, water vapor, and energetic electron irradiation on the intrinsic properties of perovskites is important in the development of perovskite-based solar cells. Various phase transition and degradation processes have been reported when these agents interact with perovskites separately. However, detailed studies of their synergistic effects are still missing. In this work, the synergistic effect of three factors (exposure to laser light, water vapor, and e-beam) on the optical and physical properties of two-dimensional (2D) Ruddlesden-Popper (RP) perovskite flakes [(BA)2(MA)2Pb3Br10] has been investigated in an environmental cell. When the perovskite flakes were subjected to moderate laser irradiation in a humid environment after prior e-beam irradiation, the photoluminescence (PL) peak centered at 480 nm vanished, while a new PL peak centered at 525 nm emerged, grew, and then quenched. This indicates the degradation process of the 2D RP perovskite was a phase transition to a three-dimensional (3D) perovskite [MAPbBr3] followed by the degradation of 3D perovskite. The spatial distribution of the 525 nm PL signal shows that this phase-transition process spreads across the flake to the area as far as ∼40 µm from the laser spot. Without humidity, the phase transition happened in the laser-irritated area but did not spread, which suggests that moisture enhanced the ion migration from the laser-scanned area to the rest of the flake and accelerated the phase transition in the nearby area. Experiments with no prior e-beam irradiation show that e-beam irradiation is the key to activating the 2D-3D phase transition. Therefore, when the three factors work synergistically, a conversion from the 2D RP perovskite into the 3D perovskite is not localized and propagates through the perovskite. These findings contribute to our understanding of the complex interactions between external stimuli and perovskite materials, thereby advancing the development of efficient and stable perovskite-based solar cells.

Valacyclovir and Acyclovir Are Substrates of the Guanine Deaminase Cytosolic PSD-95 Interactor (Cypin).

Valacyclovir, enzymatically hydrolyzed in the body to acyclovir, is a guanine-based nucleoside analog commonly prescribed as an antiviral therapy. Previous reports suggest that guanosine analogs bind to guanine deaminase; however, it is unclear whether they act as inhibitors or substrates. Data from our laboratory suggest that inhibition of guanine deaminase by small molecules attenuates spinal cord injury-induced neuropathic pain. Here, we examine whether the guanosine analogs valacyclovir and acyclovir are deaminated by cypin (cytosolic PSD-95 interactor), the major guanine deaminase in the body, or if they act as cypin inhibitors. Using purified Rattus norvegicus cypin, we use NADH-coupled assay to confirm deamination of valacyclovir and determined Michaelis-Menten constants. Subsequently, we use tryptophan fluorescence quenching assay to calculate dissociation constants for valacyclovir and acyclovir and find that inclusion of the valine motif in valacyclovir increases affinity for cypin compared to acyclovir. To our knowledge, neither Km nor KD values for cypin has been previously reported for either compound. We use Amplex Red assay and demonstrate that both valacyclovir and acyclovir are cypin substrates and that their metabolites are further processed by xanthine oxidase and uricase. Using molecular dynamics simulations, we demonstrate that an alpha helix near the active site is displaced when valacyclovir binds to cypin. Furthermore, we used LC-MS-based assay to directly confirm deamination of valacyclovir by cypin. Taken together, our results demonstrate a novel role for cypin in deamination of valacyclovir and acyclovir and suggest that therapeutics based on purine structures may be inactivated by cypin, decreasing inhibitory efficacy.

Curve progression following selective and nonselective spinal fusion for adolescent idiopathic scoliosis: are selective fusions stable?

PURPOSE: The purpose of this study is to compare postoperative outcomes between selective and non-selective fusions longitudinally over the first five postoperative years. METHODS: Patient parameters were retrieved from a multicenter, prospective, database. Patients with Lenke 1-6, B and C deformities were included. Patients were stratified into 2 groups: selective fusion (SF), if the last instrumented vertebra (LIV) was at or cranial to the lumbar apex, or non-selective fusion (NSF). Differences in coronal and sagittal radiographic outcomes were assessed with generalized linear models (GLMs) at 1-, 2- and 5- year postoperative outcomes. Five-year postoperative categorical radiographic outcomes, flexibility, scoliosis research society scores (SRS), and reoperation rates were compared between groups. Matched cohorts were created for subgroup analysis. RESULTS: 416 (SF:261, NF:155) patients, including 353 females were included in this study. The mean preoperative thoracic and lumbar Cobb angles were 57.3 ± 8.9 and 45.3 ± 8.0, respectively. GLMs demonstrated greater postoperative coronal deformity in the SF group (p < 0.01); however, the difference between groups did not change overtime (p > 0.05) indicating a relatively stable postoperative deformity correction. The SF group had a greater incidence of lumbar Cobb ≥ 26 degrees (p < 0.01). The NSF group demonstrated worse forward and lateral flexibility at 5-year postoperative outcome (p < 0.05). There was no difference in postoperative SRS scores between the SF and NSF groups. Reoperation rates were similar between groups. CONCLUSION: Selective fusion results in greater coronal plane deformity; however, this deformity does not progress significantly over time compared to non-selective fusion. Selective spinal fusion may be a beneficial option for a larger subset of patients than previously identified. LEVEL OF EVIDENCE: III.

Retrospective Seroprevalence of Orthopoxvirus Antibodies among Key Populations, Kenya.

We identified a cluster of mpox exposures among key populations in Kenya through retrospective serologic screening. We identified strong seropositivity among sex workers and gay, bisexual, and other men who have sex with men. These findings demonstrate the need for increased mpox surveillance among mpox-endemic and mpox-endemic-adjacent regions in Africa.

Interplay between Copper, Phosphatidylserine, and α-Synuclein Suggests a Link between Copper Homeostasis and Synaptic Vesicle Cycling.

Copper homeostasis is critical to the functioning of the brain, and its breakdown is linked with many brain diseases. Copper is also known to interact with the negatively charged lipid, phosphatidylserine (PS), as well as α-synuclein, an aggregation-prone protein enriched in the synapse, which plays a role in synaptic vesicle docking and fusion. However, the interplay between copper, PS lipid, and α-synuclein is not known. Herein, we report a detailed and predominantly kinetic study of the interactions among these three components pertinent to copper homeostasis and neurotransmission. We found that synaptic vesicle-mimicking small unilamellar vesicles (SUVs) can sequester any excess free Cu2+ within milliseconds, and bound Cu2+ on SUVs can be reduced to Cu+ by GSH at a nearly constant rate under physiological conditions. Moreover, we revealed that SUV-bound Cu2+ does not affect the binding between wild-type α-synuclein and SUVs but affect that between N-terminal acetylated α-synuclein and SUVs. In contrast, Cu2+ can effectively displace both types of α-synuclein from the vesicles. Our results suggest that synaptic vesicles may mediate copper transfer in the brain, while copper could participate in synaptic vesicle docking to the plasma membrane via its regulation of the interaction between α-synuclein and synaptic vesicle.

Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention.

BACKGROUND: 1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown. METHODS: Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA. CONCLUSIONS: Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.